Interpenetrating network hydrogel-loaded embryonic stem cell-derived endocardial cells improves cardiac function after myocardial infarction

BACKGROUND: With an in-depth understanding of cardiac cell differentiation, cell therapy derived from stem cells has shown promising therapeutic effects in the treatment of myocardial infarction (MI). Although many types of cardiac or noncardiac cells have been found to play protective roles in MI, the specific role of endocardial cells (ECCs) in MI has not been reported. METHODS: The current study was designed to determine whether human embryonic stem cell (hESC)-derived endocardial cells (hESC-ECCs) could be protective against MI. We first developed a cell delivery system by constructing a photosensitive interpenetrating network hydrogel consisting of gelatin methacryloyl (GelMA) and silk fibroin methacryloyl (SilMA). The sorted hESC-ECCs were loaded into the delivery system and then injected into the pericardium cavity of the MI rats. RESULTS: These results show that the cell delivery system has good biocompatibility. Moreover, the delivered endocardial cells improved cardiac function and delayed capillary atrophy after MI. Further mechanistic analysis revealed that hESC-ECCs protect the mitochondria of cardiomyocytes from damage under oxidative stress and potentially promote the angiogenesis of cardiac endothelial cells. CONCLUSION: Our results demonstrated that hESC-ECCs have the potential to serve as a cell therapy strategy for MI treatment by maintaining cardiomyocyte survival and facilitating angiogenesis.